Loading of erythropoietin on biphasic calcium phosphate bioceramics promotes osteogenesis and angiogenesis by regulating EphB4/EphrinB2 molecules

Yu Wang,Peng Wang,Zichao Xiang,Zhifan Qin,Jihua Li,Yuxian Chu,Qionghui Wu

doi:10.1007/s10856-022-06644-9

Abstract

Improving osteogenesis and angiogenesis using different cells and drugs is critical in the field of bone tissue engineering. Recent research has found that erythropoietin (EPO) plays an important role in both osteogenesis and angiogenesis. In this study, we grafted polydopamine and EPO onto the surface of biphasic calcium phosphate. The characterization and release property of the modified bioceramics were assessed. Cell proliferation, expression of osteoblastic and endothelial markers, and EphB4/EphrinB2 molecules were investigated while employing co-cultures of two different cells [rat vein endothelial cells (VECs) and rat bone marrow mesenchymal stromal cells (BMSCs)]. The modified bioceramics were finally implanted into the SD rats’ femurs and followed by investigating the bone defect repair efficacy and the expression of EphB4/EphrinB2 molecules in vivo. The results indicated that the modified bioceramics could control the release of EPO continuously. The osteogenesis and angiogenesis were improved along with the increased expression of EphB4/EphrinB2 molecules. The expression of EphB4/EphrinB2 molecules was also significantly increased in vivo and the bone defect was repaired effectively. Overall, our findings demonstrated that EPO loading on biphasic calcium phosphate bioceramics could promote both osteogenesis and angiogenesis. The results suggest that EphB4/EphrinB2 may be crucial in the process.Graphical abstract

Highlights

Calcium phosphate ceramics have been used as effective bone substitutes for the repair of surgical or traumatic defects
The Biphasic calcium phosphate (BCP) bioceramics had an average porosity of 63.6% and an average pore size of 95.7 nm
The changes of the X-ray diffraction (XRD) curve preliminarily proved the successful grafting of EPO on BCP bioceramics (Fig. 2a)

Summary

Introduction

Calcium phosphate ceramics have been used as effective bone substitutes for the repair of surgical or traumatic defects. Biphasic calcium phosphate (BCP) consisting of two individual phases of calcium phosphate β-tricalcium phosphate (TCP) and hydroxyapatite (HA) in variable proportions is bioactive and similar with the natural bone in inorganic composition [1, 2]. A growing number of studies have suggested that surface modification of bioceramics with 19 Page 2 of 15. Bioceramic surface compositions can influence cell functions including cell attachment, differentiation, and proliferation [3,4,5]. Different methods of surface modifications including physical, chemical and treatments have been used to improve bioceramics’ surface physicochemical properties and cellular bioactivity [6,7,8]. Typical proteins like BMP-7 and bone morphogenetic protein-2 have been widely investigated for improving the bone formation of bioceramics [4, 5, 9, 10]

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